Composition and medical product for reducing body weight and body fat, and use of said product

ABSTRACT

Provided is a plant extract composition and a pharmaceutical composition thereof for reducing body weight and body fat, wherein the plant extract composition comprises a green tea extract and a turmeric extract respectively 30 wt % to 75 wt % and 20 wt % to 55 wt % of a total weight of the composition. In diet-induced obesity models, either obesity is induced first or simultaneously with administration, the plant extract composition and a pharmaceutical composition thereof can reduce body weight and body fat more significantly than a single plant extract or commercially available weight loss drugs.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a Continuation of U.S. patent applicationSer. No. 15/936,695, filed Mar. 27, 2018, which claims the benefit ofpriority to U.S. Provisional Patent Application No. 62/477,514, filedMar. 28, 2017, and is a Continuation-in-part of U.S. patent applicationSer. No. 15/025,898, filed Mar. 30, 2016, which is a U.S. National StageEntry of International Application No. PCT/CN2015/088338, filed Aug. 28,2015, which claims the benefit of priority to U.S. Provisional PatentApplication No. 62/042,955, filed Aug. 28, 2014, the contents of each ofwhich are incorporated herein by reference in their entireties.

INCORPORATION OF SEQUENCE LISTING

A computer readable_text file, entitled “Caliway—70001US04_ST25” createdon or about Feb. 28, 2020, with a file size of about 0.926 KB, containsthe sequence listing for this application and is hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

The present invention relates to a composition, especially a compositioncomprises epigallocatechin gallate (EGCG), curcumin, and an excipient;the present invention relates to an application of said composition,especially an application in preparing a pharmaceutical composition forreducing body weight and body fat with said composition; the presentinvention relates to a pharmaceutical composition comprising saidcomposition, especially a pharmaceutical composition for reducing bodyweight and body fat; the present invention further relates to anapplication of said pharmaceutical composition, especially anapplication for reducing body fat, reducing body weight, treating fattyliver, or treating non-alcoholic steatohepatitis with effective doses ofsaid pharmaceutical composition.

BACKGROUND OF THE INVENTION

Obesity is a body condition in which accumulation of excessive body fatcauses adverse effects on health, thereby potentially leading toshortened lifespan and various health problems. According to thedefinition of obesity by World Health Organization, a body mass index(BMI) greater than 25 is defined as overweight, and a BMI greater than30 is defined as obese. Some Eastern Asian countries adopt strictercriteria. For example, the Ministry of Health and Welfare of Taiwanannounced in April 2002 that a Taiwanese adult with BMI≥27 is consideredobese, and 24≤BMI<27 is considered overweight.

The statistics show that the worldwide overweight and obese populationhas exceeded 2.7 billion people in 2014. Among them, approximately 13%are obese, and these obese people are at significantly higher risk ofrelated diseases such as cardiovascular disease, hyperlipidemia, fattyliver, non-alcoholic steatohepatitis, cirrhosis, diabetes, and cancer.

Current synthetic drugs for reducing body fat or body weight stillpresent cardiovascular risks and safety concerns to various extents. Onthe other hand, plant extract ingredients for reducing body fat or bodyweight often face the issue of low bioavailability and thus lowefficacy. Therefore, the market is in dire need of a drug for reducingbody fat and body weight with better safety profile, less side effects,no cardiovascular risks, and high bioavailability, that can effectivelyreduce body weight and body fat and lower the risks to cardiovasculardisease.

SUMMARY OF THE INVENTION

Because of the drawback of the traditional art, the present inventionprovides a plant extract composition for reducing body weight and bodyfat. Said composition comprises green tea extract and turmeric extract,and the weight percentages of the green tea extract and the turmericextract are 30% to 75% and 20% to 55%, respectively, based on the totalweight of the plant extract composition. Alternatively, the weightpercentages of the green tea extract and the turmeric extract are 20% to91% and 9% to 80%, respectively, based on the total weight of the plantextract composition. Preferably, the weight percentages of the green teaextract and the turmeric extract are 40% to 67% and 33% to 60%,respectively.

Preferably, the weight ratio of the green tea extract to the turmericextract in the plant extract composition is 1:4 to 10:1. Preferably, theweight ratio of the green tea extract to the turmeric extract is 2:3 to2:1.

Preferably, the plant extract composition of the present inventionfurther comprises resveratrol, and the resveratrol is greater than 0% byweight (hereinafter referred to as “wt %”) and up to 30 wt % of thetotal weight of said composition.

In the present invention, turmeric extract refers to a mixture ofturmeric ingredients extracted by any solvent and any extraction method,commercially available turmeric extract, any mixture containing morethan 75 wt % curcumin, any mixture containing more than 75 wt %curcuminoid, or commercially available curcumin.

In the present invention, resveratrol refers to resveratrol extractedfrom natural plants or commercially available resveratrol. Preferably,the purity of resveratrol is 90% to 100% (in weight percentage).

In the present invention, green tea extract refers to a green teaingredient mixture extracted by any solvent and any extraction method,or commercially available green tea extract. Preferably, it refers to amixture containing at least 45 wt % epigallocatechin gallate (EGCG), anymixture containing at least 90 wt % catechins, or commercially availableepigallocatechin gallate (EGCG).

Preferably, the weight percentages of catechins and curcumin are 20% to91% and 9% to 80%, respectively, based on the total weight of the plantextract composition. Preferably, the weight percentages of catechins andcurcumin are 40% to 67% and 33% to 60%, respectively.

Preferably, the weight ratio of catechins to curcumin in the plantextract composition is 1:4 to 10:1. Preferably, the weight ratio ofcatechins to curcumin is 2:3 to 2:1.

The present invention further provides a composition for reducing bodyweight or body fat, comprising:

-   -   an excipient; and    -   an active ingredient composition for reducing body weight or        body fat, and the active pharmaceutical ingredient composition        for reducing body weight or body fat comprises epigallocatechin        gallate (EGCG) and curcumin.    -   Wherein, the excipient comprises at least one of glyceryl        dibehenate, polyoxyethylene stearates, polysorbate 80 mixture,        vitamin E polyethylene glycol succinate, glyceryl monostearate,        and oleoyl polyoxyl-6 glycerides, or a combination thereof        additionally, the polysorbate 80 mixture comprises polysorbate        80 and magnesium aluminometasilicate.

Preferably, the composition for reducing body weight or body fat furthercomprises at least one of glyceryl palmitostearate, polysorbate 20,poloxamer, and polyethylene glycols (PEG), or a combination thereof.

Preferably, the composition for reducing body weight or body fat furthercomprises piperine.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the weight percentage of the polyoxyethylene (32) stearateis 0.1%-20% based on the total weight of the composition for reducingbody weight or body fat; alternatively, the weight percentage of thepolysorbate 80 mixture is 0.5%-20% based on the total weight of thecomposition for reducing body weight or body fat; alternatively, saidpolyoxyethylene stearate is polyoxyethylene (40) stearate, and theweight percentage of the polyoxyethylene (40) stearate is 0.005%-6.7%based on the total weight of the composition for reducing body weight orbody fat.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the weight percentage of the polyoxyethylene (32) stearateis 1%-15% based on the total weight of the composition for reducing bodyweight or body fat; alternatively, the weight percentage of thepolysorbate 80 mixture is 1%-15% based on the total weight of thecomposition for reducing body weight or body fat; alternatively, saidpolyoxyethylene stearate is polyoxyethylene (40) stearate, and theweight percentage of the polyoxyethylene (40) stearate is 0.01%-3.3%based on the total weight of the composition for reducing body weight orbody fat.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the weight percentage of the polyoxyethylene (32) stearateis 1%-10% based on the total weight of the composition for reducing bodyweight or body fat; alternatively, the weight percentage of thepolysorbate 80 mixture is 3%-10% based on the total weight of thecomposition for reducing body weight or body fat; alternatively, saidpolyoxyethylene stearate is polyoxyethylene (40) stearate, and theweight percentage of the polyoxyethylene (40) stearate is 0.05%-1% basedon the total weight of the composition for reducing body weight or bodyfat.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the value of the ratio of the weight of the curcumin tothe weight of the polyoxyethylene (32) stearate is 5.3-26.7;alternatively, the value of the ratio of the weight of the curcumin tothe weight of the polysorbate 80 mixture is 2-8.9; alternatively, thepolyoxyethylene stearate is polyoxyethylene (40) stearate, and the valueof the ratio of the weight of the curcumin to the weight of thepolyoxyethylene (40) stearate is 40-533.3; alternatively, thepolyoxyethylene stearate is polyoxyethylene (32) stearate, and the valueof the ratio of the weight of the active ingredient composition forreducing body weight or body fat to the weight of the polyoxyethylene(32) stearate is 9.5-47.5; alternatively, the value of the ratio of theweight of the active ingredient composition for reducing body weight orbody fat to the weight of the polysorbate 80 mixture is 3.6-15.8;alternatively, the polyoxyethylene stearate is polyoxyethylene (40)stearate, and the value of the ratio of the weight of the activeingredient composition for reducing body weight or body fat to theweight of the polyoxyethylene (40) stearate is 71.3-950.

Preferably, the composition for reducing body weight or body fat furthercomprises at least one of mannitol, microcrystalline celluloses, sodiumdodecyl sulfate (SDS), and cross-linked carboxymethyl celluloses, or acombination thereof.

Preferably, the value of the ratio of the weight of the curcumin to theweight of the epigallocatechin gallate (EGCG) is 3.2-0.32;alternatively, the weight percentage of the epigallocatechin gallate(EGCG) is 23.8%-75.8%, and the weight percentage of the curcumin is24.2%-76.2%, based on the total weight of the active ingredientcomposition for reducing body weight or body fat.

Preferably, the value of the ratio of the weight of the curcumin to theweight of the epigallocatechin gallate is 3.2-0.4; alternatively, theweight percentage of the epigallocatechin gallate is 23.8%-71.4%, andthe weight percentage of the curcumin is 28.6%-76.2%, based on the totalweight of the active ingredient composition for reducing body weight orbody fat.

Preferably, the active ingredient composition for reducing body weightor body fat further comprises resveratrol.

The active ingredient composition for reducing body weight or body fatdescribed in the present invention refers to a combination of at leasttwo ingredients that can reduce body weight or visceral fat of anindividual when the ingredient are administered to the individualsingly.

The present invention further provides a method for reducing body weightor body fat of an individual, comprising administering a composition toan individual, wherein the composition comprises

-   -   an excipient; and    -   an active ingredient composition for reducing body weight or        body fat, and the active ingredient composition for reducing        body weight or body fat comprises epigallocatechin gallate        (EGCG) and curcumin.    -   Wherein, the excipient comprises at least one of glyceryl        dibehenate, polyoxyethylene stearates, polysorbate 80 mixture,        vitamin E polyethylene glycol succinate, glyceryl monostearate,        and oleoyl polyoxyl-6 glycerides, or a combination thereof;        additionally, the polysorbate 80 mixture comprises polysorbate        80 and magnesium aluminometasilicate.

Preferably, the composition further comprises at least one of glycerylpalmitosterate, polysorbate 20, poloxamer, and polyethylene glycols(PEG), or a combination thereof.

Preferably, the composition further comprises piperine.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the weight percentage of the polyoxyethylene (32) stearateis 0.1%-20% based on the total weight of the composition; alternatively,the weight percentage of the polysorbate 80 mixture is 0.5%-20% based onthe total weight of the composition; alternatively, the polyoxyethylenestearate is polyoxyethylene (40) stearate, and the weight percentage ofthe polyoxyethylene (40) stearate is 0.005%-6.7% based on the totalweight of the composition.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the weight percentage of the polyoxyethylene (32) stearateis 1%-15% based on the total weight of the composition; alternatively,the weight percentage of the polysorbate 80 mixture is 1%-15% based onthe total weight of the composition; alternatively, the polyoxyethylenestearate is polyoxyethylene (40) stearate, and the weight percentage ofthe polyoxyethylene (40) stearate is 0.01%-3.3% based on the totalweight of the composition.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the weight percentage of the polyoxyethylene (32) stearateis 1%-10% based on the total weight of the composition; alternatively,the polysorbate 80 mixture is 3%-10% based on the total weight of thecomposition; alternatively, the polyoxyethylene stearate ispolyoxyethylene (40) stearate, and the weight percentage of thepolyoxyethylene (40) stearate is 0.05%-1% based on the total weight ofthe composition.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the value of the ratio of the weight of the curcumin tothe weight of the polyoxyethylene (32) stearate is 5.3-26.7;alternatively, the value of the ratio of the weight of the curcumin tothe weight of the polysorbate 80 mixture is 2-8.9; alternatively, thepolyoxyethylene stearate is polyoxyethylene (40) stearate, and the valueof the ratio of the weight of the curcumin to the weight of thepolyoxyethylene (40) stearate is 40-533.3; alternatively, thepolyoxyethylene stearate is polyoxyethylene (32) stearate, and the valueof the ratio of the weight of the active ingredient composition forreducing body weight or body fat to the weight of the polyoxyethylene(32) stearate is 9.5-47.5; alternatively, the value of the ratio of theweight of the active ingredient composition for reducing body weight orbody fat to the weight of the polysorbate 80 mixture is 3.6-15.8;alternatively, the polyoxyethylene stearate is polyoxyethylene (40)stearate, and the value of the ratio of the weight of the activeingredient composition for reducing body weight or body fat to theweight of the polyoxyethylene (40) stearate is 71.3-950.

Preferably, wherein the composition further comprises at least one ofmannitol, microcrystalline celluloses, sodium dodecyl sulfate, andcross-linked carboxymethyl celluloses, or a combination thereof.

Preferably, the value of the ratio of the weight of the curcumin to theweight of the epigallocatechin gallate is 3.2-0.32; alternatively, theweight percentage of the epigallocatechin gallate is 23.8%-75.8%, andthe weight percentage of the curcumin is 24.2%-76.2%, based on the totalweight of the active ingredient composition for reducing body weight orbody fat.

Preferably, the value of the ratio of the weight of the curcumin to theweight of the epigallocatechin gallate is 3.2-0.4; alternatively, theweight percentage of the epigallocatechin gallate is 23.8%-71.4%, andthe weight percentage of the curcumin is 28.6%-76.2%, based on the totalweight of the active ingredient composition for reducing body weight orbody fat.

Preferably, the active ingredient composition for reducing body weightor body fat further comprises resveratrol.

Preferably, the composition is administered to the individual orally.

Preferably, the individual is an individual with normal body weight, anoverweight individual, an obese individual, an individual with fattyliver, or an individual with non-alcoholic steatohepatitis (NASH).

The present invention further provides a method for treating fatty liveror non-alcoholic steatohepatitis, comprising administering a compositionto an individual with fatty liver or non-alcoholic steatohepatitis,wherein the composition comprises

-   -   an excipient; and    -   an active ingredient composition for reducing body weight or        body fat, and the active ingredient composition for reducing        body weight or body fat comprises epigallocatechin gallate and        curcumin;    -   wherein, the excipient comprises at least one of glyceryl        dibehenate, polyoxyethylene stearates, polysorbate 80 mixture,        vitamin E polyethylene glycol succinate, glyceryl monostearate,        and oleoyl polyoxyl-6 glycerides, or a combination thereof;        additionally, the polysorbate 80 mixture comprises polysorbate        80 and magnesium aluminometasilicate.

Preferably, the composition further comprises at least one of glycerylpalmitosterate, polysorbate 20, poloxamer, and polyethylene glycols, ora combination thereof.

Preferably, the composition further comprises piperine.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the weight percentage of the polyoxyethylene (32) stearateis 0.1%-20% based on the total weight of the composition; alternatively,the weight percentage of the polysorbate 80 mixture is 0.5%-20% based onthe total weight of the composition; alternatively, the polyoxyethylenestearate is polyoxyethylene (40) stearate, and the weight percentage ofthe polyoxyethylene (40) stearate is 0.005%-6.7% based on the totalweight of the composition.

Preferably, the polyoxyethylene stearate is polyoxyethylene (32)stearate, and the value of the ratio of the weight of the curcumin tothe weight of the polyoxyethylene (32) stearate is 5.3-26.7;alternatively, the value of the ratio of the weight of the curcumin tothe weight of the polysorbate 80 mixture is 2-8.9; alternatively, thepolyoxyethylene stearate is polyoxyethylene (40) stearate, and the valueof the ratio of the weight of the curcumin to the weight of thepolyoxyethylene (40) stearate is 40-533.3; alternatively, thepolyoxyethylene stearate is polyoxyethylene (32) stearate, and the valueof the ratio of the weight of the active ingredient composition forreducing body weight or body fat to the weight of the polyoxyethylene(32) stearate is 9.5-47.5; alternatively, the value of the ratio of theweight of the active ingredient composition for reducing body weight orbody fat to the weight of the polysorbate 80 mixture is 3.6-15.8;alternatively, the polyoxyethylene stearate is polyoxyethylene (40)stearate, and the value of the ratio of the weight of the activeingredient composition for reducing body weight or body fat to theweight of the polyoxyethylene (40) stearate is 71.3-950.

Preferably, wherein the composition further comprises at least one ofmannitol, microcrystalline celluloses, sodium dodecyl sulfate, andcross-linked carboxymethyl celluloses, or a combination thereof.

Preferably, the value of the ratio of the weight of the curcumin to theweight of the epigallocatechin gallate is 3.2-0.32; alternatively, theweight percentage of the epigallocatechin gallate is 23.8%-75.8%, andthe weight percentage of the curcumin is 24.2%-76.2%, based on the totalweight of the active ingredient composition for reducing body weight orbody fat.

Preferably, the value of the ratio of the weight of the curcumin to theweight of the epigallocatechin gallate is 3.2-0.4; alternatively, theweight percentage of the epigallocatechin gallate is 23.8%-71.4%, andthe weight percentage of the curcumin is 28.6%-76.2%, based on the totalweight of the active ingredient composition for reducing body weight orbody fat.

Preferably, the composition is administered orally to the individualwith fatty liver or non-alcoholic steatohepatitis.

The present invention further provides a method for manufacturing aplant extract composition comprising green tea extract and turmericextract, including mixing the plant extract composition comprising greentea extract and turmeric extract with a pharmaceutically acceptable saltcomposition, a pharmaceutically acceptable stabilizers or apharmaceutically acceptable excipient to produce capsules, tablets, orto manufacture coated tablets or solutions for injection or infusion.

Preferably, the method further includes adding resveratrol to obtain aplant extract composition comprising green tea extract, turmericextract, and resveratrol.

Preferably, the stabilizer includes, but is not limited to, xylitol,sorbitol, polydextrose, isomaltitol, and D-glucose.

The present invention further provides a use of said plant extractcomposition for reducing body weight and body fat in preparing apharmaceutical composition for reducing body weight and body fat.

The present invention provides a pharmaceutical composition for reducingbody weight and body fat comprising an effective dose of said plantextract composition for reducing body weight and body fat and apharmaceutically acceptable excipient.

In the preferred embodiments, said pharmaceutical composition furthercomprises an effective dose of resveratrol for reducing body weight andbody fat.

According to the present invention, said “pharmaceutically acceptableexcipient” or “excipient” includes, but is not limited to, at least oneof disintegrants, binders, fillers, lubricants, suspending agents,solubilizers, and glidants.

Preferably, said pharmaceutically acceptable excipient or excipientincludes, but is not limited to, at least one of piperine, glyceryldibehenate (also known as glyceryl monobehenate, the main ingredient ofCompritol 888 ATO), oleoyl polyoxyl-6 glycerides (also known as oleoylmacrogolglycerides, the main ingredient of Labrafil M 1944 CS), glycerolpalmitostearate (the main ingredient of Precirol ATO 5), magnesiumstearate, poloxamer 188, Labrasol, Poloxamer 407, polyethylene glycol6000 (PEG 6000), glyceryl monostearate (the main ingredient of IMWITOR491), sodium dodecyl sulfate (SDS), Sepitrap 80 (a polysorbate 80mixture, comprising polysorbate 80 and magnesium aluminometasilicate),polyethylene glycol 400 (PEG 400), polysorbate 20, polyoxyethylenestearates, polyoxyethylene (32) stearate (the main ingredient ofGelucire® 48/16), polyoxyethylene (40) stearate, and vitamin Epolyethylene glycol succinate (the main ingredient of TPGS), or acombination thereof. The amount of excipient used depends on the amountof active ingredient used and the formulation, and one type of excipientcan perform more than one function.

Preferably, in the embodiments of the present invention where glyceryldibehenate was added refers to examples such as directly adding glyceryldibehenate or adding Compritol 888 ATO; in the embodiments of thepresent invention where oleoyl polyoxyl-6 glycerides were added refersto examples such as directly adding oleoyl polyoxyl-6 glycerides oradding Labrafil M 1944 CS; in the embodiments of the present inventionwhere glycerl palmitostearate was added refers to examples such asdirectly adding glyceryl palmitostearate or adding Precirol ATO 5; inthe embodiments of the present invention where glyceryl monostearate wasadded refers to examples such as directly adding glyceryl monostearateor adding IMWITOR 491; in the embodiments of the present invention wherepolysorbate 80 mixture was added refers to examples such as adding anymixture comprising polysorbate 80 and magnesium aluminometasilicate oradding Sepitrap 80; in the embodiments of the present invention wherepolyoxyethylene (32) stearate was added refers to examples such asdirectly adding polyoxyethylene (32) stearate or adding Gelucire® 48/16;in the embodiments where vitamin E polyethylene glycol succinate wasadded refers to examples such as directly adding vitamin E polyethyleneglycol succinate or adding TPGS.

Preferably, based on the total weight of the composition, the weightpercentage of excipient is 10%-60%.

Preferably, based on the total weight of the composition, the weightpercentage of piperine is 0.1%-1%.

Preferably, based on the total weight of the composition, the weightpercentage of glyceryl dibehenate is 1%-10%. Preferably, the weightpercentage of glyceryl dibehenate is 1%-3%.

Preferably, based on the total weight of the composition, the weightpercentage of oleoyl macrogolglycerides is 10%-99%.

Preferably, based on the total weight of the composition, the weightpercentage of glyceryl palmitostearate is 1%-3%.

Preferably, based on the total weight of the composition, the weightpercentage of magnesium stearate is 0%-2%. Preferably, the weightpercentage of magnesium stearate is 0%-0.5%.

Preferably, based on the total weight of the composition, the weightpercentage of poloxamer 188 is 0.01%-10%.

Preferably, based on the total weight of the composition, the weightpercentage of poloxamer 407 is 0.01%-10%.

Preferably, based on the total weight of the composition, the weightpercentage of Labrasol is 10%-99%. Preferably, the weight percentage ofLabrasol is 10%-35%.

Preferably, based on the total weight of the composition, the weightpercentage of PEG 6000 is 0%-5%.

Preferably, based on the total weight of the composition, the weightpercentage of IMWITOR 491 is 0.5%-2%.

Preferably, based on the total weight of the composition, the weightpercentage of sodium dodecyl sulfate is 0.5%-2.5%.

Preferably, based on the total weight of the composition, the weightpercentage of Sepitrap 80 is 0%-20%.

Preferably, said disintegrant includes at least one of agar, alginicacid, calcium carbonate, carboxymethylcelluloses, celluloses, clays,colloidal silica, croscarmellose sodium, cross-linked providone, gum,magnesium aluminum silicate, methyl celluloses, polacrilin potassium,sodium alginate, low substituted hydroxypropyl cellulose, crosslinkedpolyvinylpyrrolidone hydroxypropylcelluloses, sodium starch glycolate,starch, cross-linked carboxymethyl celluloses, cross-linkedpolyvinylpyrrolidone (also known as polyvinylpolypyrrolidone, PVPP), andL-hydroxypropyl cellulose (L-HPC) or a combination thereof.

Preferably, said binder includes, but is not limited to,microcrystalline cellulose (MCC), hydroxymethyl cellulose, hydroxypropylcellulose, water, ethanol, hydroxypropyl methylcellulose,polyvinylpyrrolidone (also known as povidone; PVP-K series),carboxymethylcellulose, Tween series, SPAN series, Vitamin E TPGS,Gelucire® 48/16, polyethylene glycol (PEG), propylene glycol,hydroxypropyl methylcellulose, and cyclodextrin series.

Preferably, said filler includes at least one of calcium carbonate,calcium phosphate, dibasic calcium phosphate, tribasic calcium sulfate,calcium carboxymethylcelluloses, celluloses, dextrin, salt, dextrose,fructose, lactitol, lactose, carbonate, magnesium oxide, maltitol,maltodextrin, maltose, sorbitol, starch, sucrose, sugar, xylitol,mannitol, glucose, powdered celluloses, and microcrystalline celluloses,or a combination thereof.

Preferably, said lubricant includes, but is not limited to, agar,calcium stearate, ethyl oleate, ethyl laurate, glycerin, glycerylpalmitostearate, hydrogenated vegetable oil, magnesium oxide, magnesiumstearate, mannitol, poloxamer, ethylene glycol, sodium benzoate, sodiumlauryl sulfate, sodium stearoyl acid, sorbitol, stearic acid, talc, zincstearate, silicon dioxide, and talc powder.

Preferably, said suspending agent includes, but is not limited to,mannitol, carboxymethyl cellulose (CMC), and CMC-Na. Preferably, saidsolubilizer includes, but is not limited to, at least one ofhydroxypropyl-beta-cyclodextrin, Tween 80, castor oil, polyethyleneglycol (PEG), poloxamer, polysorbate, sorbitan fatty acid esters (themain ingredients of the commercial product Span), vitamin E polyethyleneglycol succinate (the main ingredient of TPGS), polyoxyethylenestearates, propylene glycol, glyceryl stearate, and Sepitrap 80, or acombination thereof.

Preferably, said glidant includes, but is not limited to, materials suchas magnesium stearate, silicon dioxide, magnesium trisillicate, powderedcellulose, starch, talc, tribasic calcium phosphate, calcium silicate,magnesium silicate, colloidal silicon dioxide, and silicon hydrogel.

Said pharmaceutical composition of the present invention may exist invarious formulations. These formulations include, but are not limitedto, liquid, semi-solid, and solid pharmaceutical formulation, such asliquid solution (for example, solution for injection and solution forinfusion), dispersion, suspension, tablet, pill, powder, liposome, andsuppository. The preferred formulation depends on the expected route ofadministration and treatment application. Preferably, the pharmaceuticalcomposition of the present invention is presented in orally availableformulation or a formulation which can be injected or infused. In theembodiments of the present invention, the pharmaceutical composition forreducing body weight and body fat comprising effective dose of thecomposition of green tea extract and turmeric extract is administeredorally. The suitable and preferred oral formulations of the plantextract composition according to the present invention include pill,granule, coated tablet, capsule, and tablet, and other solid oralformulations are also within the scope of the present invention.

The preparation method of said soft capsule described in the presentinvention is as follows: mixing green tea extract and curcumin inappropriate lipid excipients (such as lecithin, beeswax, coconut oil,and palm oil, etc.) to form an oily solution comprising the ingredients;conducting a soft capsule filling process to encapsulate and mold theoily solution comprising the ingredients into a capsule membranematerial in liquid form (for example, gelatin, glycerol, or water,etc.), alternatively, making animal gelatin into thin layers andprocessing them into the outer membrane of capsules with stainless steelmolds, and filling the oily solution comprising the ingredients into theouter membrane; drying the soft capsules and conducting sorting andpackaging processes.

The present invention further provides an application for reducing bodyweight and body fat using said pharmaceutical composition, whichachieves the effect of reducing body fat and body weight byadministering effective doses of the pharmaceutical compositioncomprising the plant extract composition comprising green tea extractand turmeric extract to a recipient, and the recipient is a human or ananimal.

Preferably, the administration is oral administration or injectionadministration.

Preferably, the effective dose is 1.8 mg to 145 mg of the pharmaceuticalcomposition per day per kg of a recipient, and the recipient is a humanor an animal. Preferably, the recipient is a human.

Preferably, the effective dose is 5.4 mg to 70 mg of the pharmaceuticalcomposition per day per kg of a recipient, and the recipient is a humanor an animal. Preferably, the recipient is a human.

In the present invention, “effective dose” herein refers to theeffective dose calculated for different recipients based on Table 1 in“Estimating the maximum safe starting dose in initial clinical trialsfor therapeutics in adult healthy volunteers” published by the US Foodand Drug Administration (FDA).

In the present invention, “reducing body weight and body fat” refers tothe reduction of indices such as body weight or body fat of anindividual as compared to the obesity control group after administrationof effective doses of the composition comprising green tea extract andturmeric extract or the composition further comprising resveratrol.Reduction of body fat can be determined through administering an amountwithin a specific range of the composition comprising green tea extractand turmeric extract or the composition further comprising resveratrol,and measuring the change of the amount of fat, such as epididymal fat,perirenal fat, mesenteric fat, or groin and extraperitoneal fat within aspecific time frame.

The ingredients of the plant extract composition of the presentinvention are all extracted from plants. Experimental resultsdemonstrate that said plant extract composition described in the presentinvention does not affect appetite or the amount of food intake, nordoes it affect other safety of serum biochemistry indicators, and thusit has a better safety profile; comparing to other weight loss drugs onthe market, it is also safer and has no apparent side effects. Moreover,comparing to the methods of the prior art that reduce body weight bydecreasing calorie uptake through inhibiting appetite or blockingintestinal fat absorption, said plant extract composition described inthe present invention not only can reduce body weight, but also caneffectively inhibit the proliferation of adipocytes, increase fatmetabolism and energy expenditure, and target the fundamental causes ofobesity to ameliorate the issue of weight regain after weight loss andimprove various cardiovascular risk indicators such as blood lipid andblood sugar, etc. to reduce cardiovascular risk.

Therefore, said plant extract composition described in the presentinvention provides a safer and more effective method for reducing bodyweight and body fat against the global obesity and overweight epidemic,and may be applied to the use of related pharmaceutical compositions ordietary supplements in the future.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a bar graph showing the inhibitory effect of each group of thepresent invention on the growth of preadipocyte tested by MTT assay.

FIG. 2 is a bar graph showing the inhibitory effect of each group of thepresent invention on the growth of differentiating adipocytes tested byMTT assay.

FIG. 3 is a bar graph showing the expression of lipase in matureadipocytes of each group tested by reverse transcription polymerasechain reaction (RT-PCR).

FIG. 4 is a bar graph showing the difference in body weight gain of eachgroup of mice tested by administering drugs during obesity induction.

FIG. 5 is a bar graph showing the effect of different excipients on thedissolution rate of curcumin in the composition of the present inventiontested by dissolution testing.

FIG. 6 is a bar graph showing the effect of different concentrations ofpolyoxyethylene (40) stearate on the dissolution rate of curcumin in thecomposition of the present invention tested by dissolution testing.

FIG. 7 is a bar graph showing the effect of different concentrations ofpolysorbate 80 mixture on the dissolution rate of curcumin in thecomposition of the present invention tested by dissolution testing.

FIG. 8 is a bar graph showing the effect of different concentrations ofpolyoxyethylene (32) stearate on the dissolution rate of curcumin in thecomposition of the present invention tested by dissolution testing.

FIG. 9A is a bar graph showing the effect of the ratio of curcumin topolyoxyethylene (40) stearate in the composition of the presentinvention on the dissolution rate of curcumin tested by dissolutiontesting.

FIG. 9B is a bar graph showing the effect of the ratio of activepharmaceutical ingredient composition for reducing body weight or bodyfat to polyoxyethylene (40) stearate in the composition of the presentinvention on the dissolution rate of curcumin tested by dissolutiontesting.

FIG. 10A is a bar graph showing the effect of the ratio of curcumin topolysorbate 80 mixture in the composition of the present invention onthe dissolution rate of curcumin tested by dissolution testing.

FIG. 10B is a bar graph showing the effect of the ratio of activepharmaceutical ingredient composition for reducing body weight or bodyfat to polysorbate 80 mixture in the composition of the presentinvention on the dissolution rate of curcumin tested by dissolutiontesting.

FIG. 11A is a bar graph showing the effect of the ratio of curcumin topolyoxyethylene (32) stearate in the composition of the presentinvention on the dissolution rate of curcumin tested by dissolutiontesting.

FIG. 11B is a bar graph showing the effect of the ratio of activepharmaceutical ingredient composition for reducing body weight or bodyfat to polyoxyethylene (32) stearate in the composition of the presentinvention on the dissolution rate of curcumin tested by dissolutiontesting.

FIG. 12A is a bar graph showing the effect of compositions comprisingeach of the three different excipients on the total body weight gain ofeach group of rats tested by administering drugs during obesityinduction.

FIG. 12B is a bar graph showing the effect of the composition comprisingeach of the three different excipients on the body fat percentage ofeach group of rats tested by administering drugs during obesityinduction.

FIG. 13A is a bar graph showing the effect of compositions comprisingdifferent ratios of ingredients on the total body weight gain of eachgroup of rats tested by administering drugs during obesity induction.

FIG. 13B is a bar graph showing the effect of compositions comprisingdifferent ratios of ingredients on the body fat percentage of each groupof rats tested by administering drugs during obesity induction.

FIG. 14A is a bar graph showing the effect of the compositions of thepresent invention on the total body weight gain of rats with fatty liverand non-alcoholic steatohepatitis tested by administering drugs afterobesity induction.

FIG. 14B is a bar graph showing the effect of the compositions of thepresent invention on the body fat percentage of rats with fatty liverand non-alcoholic steatohepatitis tested by administering drugs afterobesity induction.

FIG. 15A is a bar graph showing the effect of the compositions of thepresent invention on the liver weight of rats with fatty liver andnon-alcoholic steatohepatitis tested by administering drugs afterobesity induction.

FIG. 15B is a bar graph showing the effect of the compositions of thepresent invention on the amount of liver fat of rats with fatty liverand non-alcoholic steatohepatitis tested by administering drugs afterobesity induction.

FIG. 15C is a bar graph showing the effect of the compositions of thepresent invention on the liver total cholesterol of rats with fattyliver and non-alcoholic steatohepatitis tested by administering drugsafter obesity induction.

FIG. 15D is a bar graph showing the effect of the compositions of thepresent invention on the liver triglyceride of rats with fatty liver andnon-alcoholic steatohepatitis tested by administering drugs afterobesity induction.

DETAILED DESCRIPTION OF THE INVENTION

The technical solutions to achieve the predetermined objectives of thepresent invention are further described hereinafter with theaccompanying drawings and the preferred embodiments of the presentinvention.

EXAMPLE 1 Preadipocyte Growth Inhibition Experiment

In this embodiment, 3T3-L1 preadipocytes were plated at the density of1×10⁴ cells/well in 96-well plates. With the exception of controls (thatis, the DMSO vehicle control group), different wells were respectivelyadded with 50 ppm of resveratrol, 50 ppm of turmeric extract, 80 ppm ofgreen tea extract, and 100 ppm of the plant extract compositions ME008A,ME008D, ME001, ME00C1, and ME00D1 of the present invention. Theexperiment was composed of nine groups with three replicates per group.After addition of the drugs and forty-eight hours of incubation, thegrowth condition of cells was imaged and recorded, and the growthinhibitory effect of each test substance on 3T3-L1 preadipocytes wasanalyzed by MTT assay. Wherein, each test substance was prepared in DMSOor sterile water. The plant extract composition ME008A of the presentinvention comprised 50 wt % green tea extract, 25 wt % green coffee beanextract, and 25 wt % resveratrol; ME008D comprised 40 wt % green teaextract, 45 wt % green coffee bean extract, and 15 wt % resveratrol;ME001 comprised 60 wt % green tea extract, 10 wt % turmeric extract, and30 wt % resveratrol; ME00C1 comprised 40 wt % green tea extract, 50 wt %turmeric extract, and 10 wt % resveratrol; ME00D1 comprised 75 wt %green tea extract and 25 wt % turmeric extract. The data of each groupare expressed as mean±SD. Letters a, b, c, d, e, f, and g indicate theresults of statistical analysis, wherein different letters indicatesignificant statistical difference between groups (p<0.05), andidentical letters indicate no significant statistical difference betweengroups (p>0.05).

Results are shown in FIG. 1. Comparing to the control group, threegroups of plant extract compositions ME00C1, ME001, and ME008D of thepresent invention all significantly inhibited the growth ofpreadipocytes (p<0.05). Among them, ME00C1 demonstrated the best growthinhibitory effect on preadipocytes (p<0.05), and the growth inhibitoryeffect of the ME00C1 composition on preadipocytes was significantlybetter than that of resveratrol, turmeric extract, or green tea extractadministered alone (p<0.05).

EXAMPLE 2 Differentiating Adipocyte Growth Inhibition Experiment

In this embodiment, 3T3-L1 preadipocytes were plated at a density of1×10⁵ cells/well in 12-well plates. On day four of culture, the mediumwas replaced with medium comprising 5 μg/ml of the differentiationinducer insulin, 1 μM of dexamethasone, and 0.5 mM of3-isobutyl-1-methylxanthine to induce adipocyte differentiation. Withthe exception of the control group (that is, the DMSO vehicle controlgroup), each group was respectively added with 50 ppm of resveratrol, 50ppm of turmeric extract, 80 ppm of green tea extract, and 100 ppm of theplant extract compositions ME008A, ME008D, ME001, MEOOC1, and ME00D1 ofthe present invention for experimentation. The experiment was composedof nine groups with three replicates per group. After addition of thedrugs and forty-eight hours of incubation, the growth situation of cellswas imaged and recorded, and the inhibitory effect of each testsubstance on differentiating adipocytes was analyzed by MTT assay. Thedata of each group are expressed as mean±SD. Letters a, b, c, d, e, andf indicate the results of statistical analysis, wherein differentletters indicate significant statistical difference between groups(p<0.05), and identical letters indicate no significant statisticaldifference between groups (p>0.05).

Results are shown in FIG. 2. Comparing to the control group, every plantextract composition of the present invention significantly inhibited thegrowth of differentiating adipocytes (p<0.05). Among them, ME00C1demonstrated the best growth inhibitory effect on differentiatingadipocytes (p<0.05), and the growth inhibitory effect on differentiatingadipocyte of the composition ME00C1 was significantly better than thatof resveratrol, turmeric extract, or green tea extract administeredalone (p<0.05).

EXAMPLE 3 Gene Expression Level of Hormone Sensitive Lipase in MatureAdipocytes Experiment

In this embodiment, 3T3-L1 cells were plated at a density of 3×10⁴cells/well in 12-well plates. On day four of culturing, the medium wasreplaced with DMEM medium (Gibco Inc, Germany) comprising 5 μg/ml ofinsulin, 1 μM of dexamethasone, and 0.5 mM of3-isobutyl-1-methylxanthine. After two days of culturing, the medium wasreplaced with medium comprising 5 μg/ml of insulin and cultured foranother 6 days. Once 3T3-L1 cells were differentiated and matured, withthe exception of the control group (that is, the DMSO vehicle controlgroup), each group was respectively added with 50 ppm of turmericextract, 50 ppm of green tea extract, and 50 ppm of plant extractcompositions of the present invention C15, C14, C13, C12, C11, D11, D12,D13, D14, and D15 for experimentation. The experiment was composed ofthirteen groups with three replicates per group. Wherein, please referto Table 1, the plant extract composition C15 of the present inventioncomprised 20 wt % green tea extract and 80 wt % turmeric extract, C14comprised 33 wt % green tea extract and 67 wt % turmeric extract, C13comprised 40 wt % green tea extract and 60 wt % turmeric extract, C12comprised 50 wt % green tea extract and 50 wt % turmeric extract, C11comprised 60 wt % green tea extract and 40 wt % turmeric extract, D11comprised 67 wt % green tea extract and 33 wt % turmeric extract, D12comprised 75 wt % green tea extract and 25 wt % turmeric extract, D13comprised 80 wt % green tea extract and 20 wt % turmeric extract, D14comprised 83 wt % green tea extract and 17 wt % turmeric extract, andD15 comprised 91 wt % green tea extract and 9 wt % turmeric extract.After addition of the drugs and seventy-two hours of incubation, RNA ofthe mature adipocytes was extracted by Trizol reagent (Thermo FisherScientific Inc, USA), and RT-PCR was carried out using a reversetranscription kit (Thermo Fisher Scientific Inc, USA) and a polymerasechain reaction kit (Thermo Fisher Scientific Inc, USA) to measure theexpression level of hormone sensitive lipase (HSL) in mature adipocytes.Wherein, the primers for PCR reaction were 5′-GAATATCACGGAGATCGAGG-3′(SEQ ID NO:1) and 5′-CCGAAGGGACACGGTGATGC-3′ (SEQ ID NO:2). The data ofeach group are expressed as mean±SD. Letters a, b, c, and d indicate theresults of statistical analysis, wherein different letters indicatesignificant statistical difference between groups (p<0.05), andidentical letters indicate no significant statistical difference betweengroups (p>0.05).

The results are shown in FIG. 3. Comparing to the control group, theturmeric extract group, and the green tea extract group, the plantextract compositions C11, C12, C13, C14, D11, D12, and D13 of thepresent invention all significantly increased the expression level ofhormone sensitive lipase (p<0.05), and showed synergistic effects onincreasing the expression level of hormone sensitive lipase,demonstrating an unanticipated effect. Therefore, synergy is achievedwhen the ratio of the weight of green tea extract to the weight ofturmeric extract is 1:2-4:1; that is, synergy is achieved when the valueof the ratio of the weight of green tea extract to the weight ofturmeric extract is 0.5-4. That is, synergy is achieved when the ratioof the weight of turmeric extract to the weight of green tea extract is0.25-2. The turmeric extract used in the embodiments of the presentinvention comprises at least 80% curcumin, and the green tea extractused contains at least 50% epigallocatechin gallate. Therefore, based onthe conversion of results of this embodiment, synergy is achieved whenthe value of the ratio of the weight of curcumin to the weight ofepigallocatechin gallate is 0.4-3.2, provided that the weightpercentages of curcumin is 28.57% -76.19% and the weight percentages ofepigallocatechin gallate is 23.81% -71.43%.

TABLE 1 Ratio between green Administered concentration tea extract andturmeric (ppm) of plant extract Group extract (Weight ratio) compositionControl group Ctrl — Curcumin (Cur.) Cur. 50 Green tea (Gre.) Gre. 50C11 3:2 50 C12 1:1 50 C13 2:3 50 C14 1:2 50 C15 1:4 50 D11 2:1 50 D123:1 50 D13 4:1 50 D14 5:1 50 D15 10:1  50

EXAMPLE 4 Animal Experiment I (Drug Administration During ObesityInduction)

In this experimental example, 8-week old B6 female mice wereexperimented and divided into a normal control group, an obesity controlgroup, a resveratrol group (the administered dose of resveratrol was61.5 mg/kg B.W.), a green tea extract group (the administered dose ofgreen tea extract was 123 mg/kg B.W.), and the plant extractcompositions ME001 of the present invention group (the administered doseof ME001 was 676.5 mg/kg B.W.) Five female mice were included in eachgroup for experimentation. During the experimental period, with theexception of the normal control group, the other groups were fed withhigh-fat diet for eight consecutive weeks to induce obesity symptoms,and were also fed by oral gavage with the test substance daily duringthe same eight weeks. The obesity control group was fed by oral gavagewith an equal volume of sterile water, and the difference in body weightof each group of mice was evaluated. The body weight and average foodintake of each animal were recorded weekly during the experimentalperiod. The mice were sacrificed after the experimentation. During theexperimental period of this experiment, no statistical difference(p>0.05) was observed in the weekly average food intake among the groupsof mice fed with high-fat diet. The data of each group are expressed asmean±SD. Letters a, b, and c indicate the results of statisticalanalysis, wherein different letters indicate significant statisticaldifference between groups (p<0.05), and identical letters indicate nosignificant statistical difference between groups (p>0.05).

The experimental results are shown in FIG. 4. Comparing to the obesitycontrol group, the total body weight gain of mice fed with the plantextract composition ME001 of the present invention was significantlyreduced (p<0.05), and the extent of reduction was 47.2%. Therefore, theplant extract composition ME001 of the present invention can effectivelyachieve the effect of reducing body weight (p<0.05). On the contrary,the total body weight gain of mice in the group administered withresveratrol alone did not show statistical difference (p>0.05) comparingto that of the obesity control group.

Additionally, comparing to the other groups, the plant extractcomposition ME001 of the present invention not only effectively reducedbody weight, but its efficacy was better than the groups of single plantextract (p<0.05), demonstrating its superior efficacy in reducing bodyweight.

EXAMPLE 5 Dissolution Testing I (The Effect of Different Excipients onthe Dissolution Rate of Curcumin)

In order to test the effect of excipients on the dissolution rate ofcurcumin in the composition of the present invention in the digestivetract of individuals, the inventor performed the following dissolutiontest.

The test substances of this experiment were prepared as follows:

Preparing tablets comprising 1% polyoxyethylene (32) stearate: 250 mg ofgreen tea extract, 200 mg of turmeric extract, polyoxyethylene (32)stearate, fillers, and disintegrants were added in order into a mixerfor mixing, and the dry powder was compressed into tablets to obtaintablets comprising 1% polyoxyethylene (32) stearate. The weight of eachtablet comprising 1% polyoxyethylene (32) stearate was 600 mg, and eachtablet comprising 1% polyoxyethylene (32) stearate comprised 250 mg ofgreen tea extract, 200 mg of turmeric extract, and 1 wt %polyoxyethylene (32) stearate.

Preparing tablets comprising 5% polysorbate 80 mixture: the preparationmethod was roughly the same as that of tablets comprisingpolyoxyethylene (32) stearate. The only difference was that 5%polysorbate 80 mixture was used to substitute for polyoxyethylene (32)stearate, such that each tablet comprised 5 wt % polysorbate 80 mixture.Wherein, said polysorbate 80 mixture was Sepitrap 80.

Preparing tablets comprising 0.5% polyoxyethylene (40) stearate, tabletscomprising 3% vitamin E polyethylene glycol succinate, tabletscomprising 5% polysorbate 20, tablets comprising 1% polyethylene glycol(PEG) 400, tablets comprising 1% polyethylene glycol (PEG) 6000, tabletscomprising 1% glyceryl monostearate, tablets comprising 1% oleoylpolyoxyl-6 glycerides, or tablets comprising 1% glyceryl dibehenate: thepreparation methods were roughly the same as that of tablets comprising1% polyoxyethylene (32) stearate. The only difference was thatpolyoxyethylene (40) stearate, vitamin E polyethylene glycol succinate,polysorbate 20, PEG 400, PEG 600, glyceryl monostearate, oleoylpolyoxyl-6 glycerides, or glyceryl dibehenate was used to substitute forpolyoxyethylene (32) stearate, respectively, such that each tabletcomprised 0.5 wt % polyoxyethylene (40) stearate, 3 wt % vitamin Epolyethylene glycol succinate, 5 wt % polysorbate 20, 1 wt % PEG 400, 1wt % PEG 6000,1 wt % glyceryl monostearate, 1 wt % oleoyl polyoxyl-6glycerides, or 1 wt % glyceryl dibehenate, respectively.

Preparing control group tablets: the preparation method was roughly thesame as that of tablets comprising polyoxyethylene (32) stearate. Theonly difference was that polyoxyethylene (32) stearate was omitted.

In all of the aforementioned tablets, each tablet comprised 250 mg ofgreen tea extract and 200 mg of turmeric extract, each tablet weighed600 mg, and the fillers, the disintegrants, and the binders used in thepreparation procedure of each tablet were identical.

The fillers described in this embodiment comprised at least one ofmannitol, starch, glucose, lactose, maltodextrin, dextrin,microcrystalline cellulose, sucrose, maltose, calcium carbonate, andpowdered cellulose, or a combination thereof.

The disintegrants described in this embodiment comprised at least one ofcross-linked sodium carboxymethyl cellulose, cross-linkedpolyvinylpyrrolidone, and low-substituted hydroxypropyl cellulose, or acombination thereof.

A tablet was individually placed into a dissolution medium in adissolution instrument (Apparatus 2, manufactured by SMI-LabHut Ltd,UK). The dissolution medium was 0.1N hydrochloric acid (HCl), the volumeof the dissolution medium was 900 ml, comprising 4% SDS, and thetemperature was 37±0.5° C. The dissolution test was performed at arotational speed of 100 rpm. Samples were collected at 30 minutes and 60minutes of testing. The curcumin concentration in the samples wasmeasured by high performance liquid chromatography (HPLC), and thedissolution rate of curcumin was calculated by the following method:

The total weight (grams) of dissolved curcumin in the dissolutionmedium÷the total weight (grams) of curcumin in a tablet=the dissolutionrate of curcumin

According to the criteria for dissolution testing of oral dosage formsby the US FDA, the dissolved amount of slowly dissolving or sparinglywater-soluble drugs should be no less than 85% of the labeled amount.Therefore, if the dissolution rate of curcumin from a tablet at 30minutes or 60 minutes of dissolution testing is at least 85%, the tabletmeets the criteria for oral dosage forms. Wherein, if the dissolutionrate of curcumin in the tablet is at least 85% at 30 minutes ofdissolution testing, it is referred to as rapidly dissolving.

After duplication of this experiment, it was found that the differencebetween duplicated experimental results was less than 1% for each typeof tablets.

The testing results are shown in FIG. 5. The dissolution rate ofcurcumin in the control group tablets, the tablets comprising 1%polyoxyethylene (32) stearate, the tablets comprising 0.5%polyoxyethylene (40) stearate, the tablets comprising 5% polysorbate 80mixture, the tablets comprising 3% vitamin E polyethylene glycolsuccinate, the tablets comprising 5% polysorbate 20, the tabletscomprising 1% PEG 400, tablets comprising 1% PEG 6000, the tabletscomprising 1% glyceryl monostearate, the tablets comprising 1% oleoylpolyoxyl-6 glycerides, and the tablets comprising 1% glyceryl dibehenateat 30 minutes was respectively 54.48%, 80.35%, 79.36%, 61.36%, 53.12%,41.57%, 79.75%, 63.46%, 80.50%, 76.62%, and 75.36%, where none reached85%; however, among them, the dissolution rate of the tablets comprising1% polyoxyethylene (32) stearate, the tablets comprising 0.5%polyoxyethylene (40) stearate, the tablets comprising 1% PEG 400, andthe tablets comprising 1% glyceryl monostearate was the highest, whereall of which was at 80±1%.

Therefore, polyoxyethylene (32) stearate, polyoxyethylene (40) stearate,PEG 400, and glyceryl monostearate can all make the compositioncomprising epigallocatechin gallate and curcumin in the presentinvention almost meet the criteria of rapid dissolving.

Please continue to refer to FIG. 5. The dissolution rate of curcuminfrom the control group tablets, the tablets comprising 1%polyoxyethylene (32) stearate, the tablets comprising 0.5%polyoxyethylene (40) stearate, the tablets comprising 5% polysorbate 80mixture, the tablets comprising 3% vitamin E polyethylene glycolsuccinate, the tablets comprising 5% polysorbate 20, the tabletscomprising 1% PEG 400, the tablets comprising 1% PEG 6000, the tabletscomprising 1% glyceryl monostearate, the tablets comprising 1% oleoylpolyoxyl-6 glycerides, and the tablets comprising 1% glyceryl dibehenateat 60 minutes was respectively 69.50%, 89.01%, 86.97%, 85.30%, 86.41%,71.67%, 87.68%, 80.52%, 89.14%, 86.50%, and 85.89%.

Wherein, the dissolution rate curcumin from the tablets comprising 1%polyoxyethylene (32) stearate, the tablets comprising 0.5%polyoxyethylene (40) stearate, the tablets comprising 5% polysorbate 80mixture, the tablets comprising 3% vitamin E polyethylene glycolsuccinate, the tablets comprising 1% PEG 400, the tablets comprising 1%glyceryl monostearate, the tablets comprising 1% oleoyl polyoxyl-6glycerides, and the tablets comprising 1% glyceryl dibehenate at 60minutes was greater than 85%.

Therefore, polyoxyethylene (32) stearate, polyoxyethylene (40) stearate,5% polysorbate 80 mixture, vitamin E polyethylene glycol succinate, PEG400, glyceryl monostearate, oleoyl polyoxyl-6 glycerides, and glyceryldibehenate can all make the composition comprising epigallocatechingallate and curcumin of the present invention meet the criteria for oraldosage forms and promote the bioavailability.

EXAMPLE 6 Dissolution Testing II (The Effect of Different Concentrationsof Excipients on the Dissolution Rate of Curcumin) Example 6-1

The effect of different concentrations of polyoxyethylene (40) stearateon the dissolution rate of curcumin.

Preparing tablets comprising 0.5% polyoxyethylene (40) stearate: thepreparation method was the same as that of tablets comprising 0.5%polyoxyethylene (40) stearate in Example 5.

Preparing tablets comprising 0.05% polyoxyethylene (40) stearate, ortablets comprising 0.1% polyoxyethylene (40) stearate: the preparationmethod was roughly the same as that of tablets comprising 0.5%polyoxyethylene (40) stearate in Example 5. The only difference was thateach tablet comprised 0.05 wt % or 0.1 wt % polyoxyethylene (40)stearate, respectively.

The testing results are shown in FIG. 6. The dissolution rate ofcurcumin from the tablets comprising 0.05% polyoxyethylene (40)stearate, the tablets comprising 0.1% polyoxyethylene (40) stearate, andthe tablets comprising 0.5% polyoxyethylene (40) stearate at 30 minuteswas respectively 83.13%, 84.71%, and 79.36%.

Please continue to refer to FIG. 6. The dissolution rate of curcuminfrom the tablets comprising 0.05% polyoxyethylene (40) stearate, thetablets comprising 0.1% polyoxyethylene (40) stearate, and the tabletscomprising 0.5% polyoxyethylene (40) stearate at 60 minutes wasrespectively 89.54%, 90.88%, and 86.97%, where all reached 85%.Therefore, 0.05-0.5 wt % polyoxyethylene (40) stearate can make thecomposition comprising epigallocatechin gallate (EGCG) and curcumin ofthe present invention meet the criteria for oral dosage forms, promotethe bioavailability, and at low concentrations can improve thedissolution rate of curcumin.

Example 6-2

The effect of different concentrations of polysorbate 80 mixture on thedissolution rate of curcumin

Preparing tablets comprising 5% polysorbate 80 mixture: the preparationmethod was the same as that of tablets comprising 5% polysorbate 80mixture in Example 5.

Preparing tablets comprising 3% polysorbate 80 mixture, or tabletscomprising 10% polysorbate 80 mixture: the preparation method wasroughly the same as that of tablets comprising 5% polysorbate 80 mixturein Example 5. The only difference was that each tablet comprised 3 wt %or 10 wt % of polysorbate 80 mixture, respectively.

The testing results are shown in FIG. 7. The dissolution rate ofcurcumin from the tablets comprising 3% polysorbate 80 mixture, thetablets comprising 5% polysorbate 80 mixture, and the tablets comprising10% polysorbate 80 mixture at 30 minutes was 71.76%, 61.36%, and 32.41%,respectively.

Please continue to refer to FIG. 7. The dissolution rate of curcuminfrom the tablets comprising 3% polysorbate 80 mixture, the tabletscomprising 5% polysorbate 80 mixture, and the tablets comprising 10%polysorbate 80 mixture at 60 minutes was 87.77%, 85.30%, and 49.98%,respectively. Among them, the dissolution rate of curcumin from thetablets comprising 3% polysorbate 80 mixture and the tablets comprising5% polysorbate 80 mixture at 60 minutes was greater than 85%. Therefore,3-5 wt % of polysorbate 80 mixture can make the composition comprisingepigallocatechin gallate and curcumin of the present invention meet thecriteria of oral dosage forms, promote the bioavailability, and at lowconcentrations can improve the dissolution rate of curcumin.

Example 6-3

The effect of different concentrations of polyoxyethylene (32) stearateon the dissolution rate of curcumin

Preparing tablets comprising 1% polyoxyethylene (32) stearate: thepreparation method was the same as that of tablets comprising 1 wt %polyoxyethylene (32) stearate in Example 5.

Preparing tablets comprising 3% polyoxyethylene (32) stearate, ortablets comprising 5% polyoxyethylene (32) stearate: the preparationmethod was roughly the same as that of tablets comprising 1%polyoxyethylene (32) stearate in Example 5. The only difference was thateach tablet comprised 3 wt % or 5 wt % of polyoxyethylene (32) stearate,respectively.

The testing results are shown in FIG. 8. The dissolution rate ofcurcumin from the tablets comprising 1% polyoxyethylene (32) stearate,the tablets comprising 3% polyoxyethylene (32) stearate, and the tabletscomprising 5% polyoxyethylene (32) stearate at 30 minutes was 80.35%,65.41%, and 44.74%, respectively.

Please continue to refer to FIG. 8. The dissolution rate of curcuminfrom the tablets comprising 1% polyoxyethylene (32) stearate, thetablets comprising 3% polyoxyethylene (32) stearate, and the tabletscomprising 5% polyoxyethylene (32) stearate at 60 minutes was 89.01%,88.11%, and 77.34%, respectively. Among them, the dissolution rate ofcurcumin from the tablets comprising 1% polyoxyethylene (32) stearateand the tablets comprising 3% polyoxyethylene (32) stearate at 60minutes was greater than 85%. Therefore, 1-3 wt % of polyoxyethylene(32) stearate can make the composition comprising epigallocatechingallate and curcumin of the present invention meet the criteria of oraldosage forms, promote the bioavailability, and at low concentrations canimprove the dissolution rate of curcumin.

EXAMPLE 7 Dissolution Testing III (The Effect of the Ratio of Drugs toExcipients on the Dissolution Rate of Curcumin) Example 7-1

The effect of the ratio of drugs to polyoxyethylene (40) stearate on thedissolution rate of curcumin

Preparing tablets with a curcumin to polyoxyethylene (40) stearateweight ratio of 53.3:1: the preparation method was the same as that oftablet comprising 0.5% polyoxyethylene (40) stearate in Example 5. Thetablet comprising 0.5% polyoxyethylene (40) stearate in Example 5comprised 200 mg of turmeric extract, and the turmeric extract used inthe present invention comprised at least 80% curcumin. Therefore, thetablet comprising 0.5% polyoxyethylene (40) stearate in Example 5comprised 160 mg (200 mg×80% =160 mg) of curcumin. Additionally, thetotal weight of the tablet comprising 0.5% polyoxyethylene (40) stearatein the Example 5 was 600 mg. Therefore, the contained amount ofpolyoxyethylene (40) stearate was 3 mg (600 mg×0.5%=3 mg). Therefore,the weight ratio of curcumin to polyoxyethylene (40) stearate in thetablet comprising 0.5% polyoxyethylene (40) stearate in the Example 5was 53.3:1 (160mg:3mg=53.3:1)

Preparing tablets with a curcumin to polyoxyethylene (40) stearateweight ratio of 40:1, tablets with a curcumin to polyoxyethylene (40)stearate weight ratio of 48:1, tablets with a curcumin topolyoxyethylene (40) stearate weight ratio of 200:1, tablets with acurcumin to polyoxyethylene (40) stearate weight ratio of 266.7:1, ortablets with a curcumin to polyoxyethylene (40) stearate weight ratio of533.3:1: the preparation methods were roughly the same as that oftablets comprising 0.5% polyoxyethylene (40) stearate in Example 5. Theonly difference was that the value of the ratio of the weight ofcurcumin to polyoxyethylene (40) stearate was respectively 40, 48, 200,266.7, or 533.3.

The testing results are shown in FIG. 9A. The dissolution rates ofcurcumin from the tablets with the value of the weight ratios ofcurcumin to polyoxyethylene (40) stearate being 40, 48, 53.3, 200,266.7, or 533.3 at 30 minutes were respectively 89.57%, 78.56%, 79.36%,89.00%, 84.71%, and 83.13%.

Please continue to refer to FIG. 9A. The dissolution rates of curcuminfrom the tablets with the value of the weight ratios of curcumin topolyoxyethylene (40) stearate being 40, 48, 53.3, 200, 266.7, or 533.3at 60 minutes were respectively 92.40%, 85.75%, 86.97%, 90.72wt %,90.88%, and 89.54%, where all was greater than 85%. Therefore, the valueof the weight ratios of curcumin to polyoxyethylene (40) stearate being40, 48, 53.3, 200, 266.7, or 533.3 in the tablets can make thecomposition comprising epigallocatechin gallate (EGCG) and curcumin ofthe present invention meet the criteria of oral dosage forms and promotethe bioavailability.

Please refer to FIG. 9B for the same experimental results. In FIG. 9B,“weight ratio of curcumin to polyoxyethylene (40) stearate” in FIG. 9Awas converted to “weight ratio of the active ingredient composition forreducing body weight or body fat to polyoxyethylene (40) stearate.”Furthermore, in this Example 7, the active ingredient composition forreducing body weight or body fat is a collective term for theepigallocatechin gallate in green tea extract and the curcumin inturmeric extract.

For example, when the weight ratio of curcumin to polyoxyethylene (40)stearate was 53.3:1 (that is, the aforementioned tablets with thecurcumin to polyoxyethylene (40) stearate weight ratio of 53:3.1, andthe preparation method was the same as that of tablets comprising 0.5%polyoxyethylene (40) stearate in Example 5), the tablet comprising 0.5%polyoxyethylene (40) stearate in Example 5 comprised 160 mg of curcuminand 3 mg of polyoxyethylene (40) stearate. Furthermore, the tabletcomprising 0.5% polyoxyethylene (40) stearate in Example 5 comprised 250mg of green tea extract, and the green tea extract used in the presentinvention comprised at least 50% epigallocatechin gallate. Therefore,the tablet comprising 0.5% polyoxyethylene (40) stearate in Example 5comprised 125 mg (250 mg×50%=125 mg) of epigallocatechin gallate.Therefore, the weight ratio of the active ingredient composition forreducing body weight or body fat to polyoxyethylene (40) stearate in thetablet comprising 0.5% polyoxyethylene (40) stearate was 95:1[(160mg+125mg):3 mg=95:1].

The testing results are shown in FIG. 9B. When the value of the weightratio of the active ingredient composition for reducing body weight orbody fat to polyoxyethylene (40) stearate in tablets comprisingpolyoxyethylene (40) stearate was 71.3, 85.5, 95, 356.3, 475, and 950,the dissolution rate of curcumin from the tablets at 30 minutes wasrespectively 89.57%, 78.56%, 79.36%, 89.00%, 84.71%, and 83.13%.

Please continue to refer to FIG. 9B. When the value of the weight ratioof the active ingredient composition for reducing body weight or bodyfat to polyoxyethylene (40) stearate in tablets comprisingpolyoxyethylene (40) stearate was 71.3, 85.5, 95, 356.3, 475, and 950,the dissolution rate of curcumin from the tablets at 60 minutes wasrespectively 92.40%, 85.75%, 86.97%, 90.72%, 90.88%, and 89.54%, whereall was greater than 85%. Therefore, the value of the weight ratio ofthe active ingredient composition for reducing body weight or body fatto polyoxyethylene (40) stearate of 71.3, 85.5, 95, 356.3, 475, or 950in the tablet can make the composition comprising epigallocatechingallate and curcumin of the present invention meet the criteria of oraldosage forms and promote the bioavailability.

Example 7-2

The effect of the ratio of drugs to polysorbate 80 mixture on thedissolution rate of curcumin

Preparing tablets with a curcumin to polysorbate 80 weight ratio of5.3:1: the preparation method was the same as that of tablets comprising5% polysorbate 80 mixture in Example 5. The tablet comprising 5%polysorbate 80 mixture in Example 5 comprised 200 mg of turmericextract, and the turmeric extract used in the present inventioncomprised at least 80% curcumin. Therefore, the tablet comprising 5%polysorbate 80 mixture in Example 5 comprised 160 mg (200 mg×80%=160 mg)of curcumin. Additionally, the total weight of the tablet comprising 5%polysorbate 80 mixture in Example 5 was 600 mg. Therefore, the amount ofpolysorbate 80 mixture in the tablet was 30 mg (600 mg×5%=30 mg).Therefore, the weight ratio of curcumin to polysorbate 80 mixture in thetablet comprising 5% polysorbate 80 mixture in Example 5 was 5.3:1(160mg:30 mg=5.3:1)

Preparing tablets with a curcumin to polysorbate 80 mixture weight ratioof 2:1, tablets with a curcumin to polysorbate 80 mixture weight ratioof 6.7:1, tablets with a curcumin to polysorbate 80 mixture weight ratioof 8:1, or tablets with a curcumin to polysorbate 80 mixture weightratio of 8.9:1: the preparation method was roughly the same as that oftablets comprising 5% polysorbate 80 mixture in Example 5. The onlydifference was that the value of the weight ratio of curcumin topolysorbate 80 mixture was respectively 2, 6.7, 8, or 8.9.

The testing results are shown in FIG. 10A. When the value of the weightratio of curcumin to polysorbate 80 mixture in the tablet comprisingpolysorbate 80 mixture was 2, 5.3, 6.7, 8, and 8.9, the dissolution rateof curcumin from the tablets at 30 minutes was respectively 60.64%,61.36%, 73.31%, 72.30%, and 71.76%.

Please continue to refer to FIG. 10A. When the value of the weight ratioof curcumin to polysorbate 80 mixture in the tablet comprisingpolysorbate 80 mixture was 2, 5.3, 6.7, 8, and 8.9, the dissolution rateof curcumin from the tablets at 60 minutes was respectively 86.16%,85.30%, 91.66%, 85.25%, and 87.77%, where all was greater than 85%.Therefore, the value of the weight ratio of curcumin to polysorbate 80mixture being 2, 5.3, 6.7, 8, or 8.9 in the tablet can make thecomposition comprising epigallocatechin gallate (EGCG) and curcumin ofthe present invention meet the criteria of oral dosage forms and promotethe bioavailability.

Please refer to FIG. 10B for the same experimental results. In FIG. 10B,“weight ratio of curcumin to polysorbate 80 mixture” in FIG. 9A wasconverted to “weight ratio of the active ingredient composition forreducing body weight or body fat to polysorbate 80 mixture.”Furthermore, in this Example 7, the active ingredient composition forreducing body weight or body fat is a collective term for theepigallocatechin gallate in green tea extract and the curcumin inturmeric extract.

For example, when the weight ratio of curcumin to polysorbate 80 mixturewas 5.3:1 (that is, the aforementioned tablets with the curcumin topolysorbate 80 mixture weight ratio of 5.3:1, and the preparation methodwas the same as that of tablets comprising 5% polysorbate 80 mixture inExample 5), the tablets comprising 5% polysorbate 80 mixture in Example5 comprised 160 mg of curcumin and 30 mg of polysorbate 80 mixture.Furthermore, the tablets comprising 5% polysorbate 80 mixture in Example5 comprised 250 mg of green tea extract, and the green tea extract usedin the present invention comprised at least 50% of epigallocatechingallate. Therefore, the tablet comprising 5% polysorbate 80 mixture inExample 5 comprised 125 mg (250 mg×50 wt %=125 mg) of epigallocatechingallate. Therefore, the weight ratio of active ingredient compositionfor reducing body weight or body fat to polysorbate 80 mixture in thetablet comprising 5% polysorbate 80 mixture in the Example 5 was 9.5:1[(160 mg+125 mg):30 mg=9.5:1].

The testing results are shown in FIG. 10B. When the value of the weightratio of the active ingredient composition for reducing body weight orbody fat to polysorbate 80 mixture in the tablet comprising polysorbate80 mixture was 3.6, 9.5, 11.9, 14.3, and 15.8, the dissolution rate ofcurcumin from the tablets at 30 minutes was respectively 60.64%, 61.36%,73.31%, 72.30%, and 71.76%.

Please continue to refer to FIG. 10B. When the value of the weight ratioof the active ingredient composition for reducing body weight or bodyfat to polysorbate 80 mixture in the tablet comprising polysorbate 80mixture was 3.6, 9.5, 11.9, 14.3, and 15.8, the dissolution rate ofcurcumin from the tablets at 60 minutes was respectively 86.16%, 85.30%,91.66%, 85.25%, and 87.77%, where all was greater than 85%. Therefore,the value of the weight ratio of the active ingredient composition forreducing body weight or body fat to polysorbate 80 mixture being 3.6,9.5, 11.9, 14.3, and 15.8 in the tablet can make the compositioncomprising epigallocatechin gallate and curcumin of the presentinvention meet the criteria of oral dosage forms and promote thebioavailability.

Example 7-3

The effect of the ratio of drugs to polyoxyethylene (32) stearate on thedissolution rate of curcumin

Preparing tablets with a curcumin to polyoxyethylene (32) stearateweight ratio of 5.3:1, tablets with a curcumin to polyoxyethylene (32)stearate weight ratio of 8.9:1, and tablets with a curcumin topolyoxyethylene (32) stearate weight ratio of 26.7:1: the preparationmethod was roughly the same as that of the tablet comprising 1%polyoxyethylene (32) stearate in Example 5. The only difference was thatthe weight ratio of curcumin to polyoxyethylene (32) stearate was 5.3,8.9, or 26.7, respectively.

The testing results are shown in FIG. 11A. When the value of the weightratio of curcumin to polyoxyethylene (32) stearate in the tabletcomprising polyoxyethylene (32) stearate was 5.3, 8.9, or 26.7, thedissolution rate of curcumin from the tablet at 30 minutes wasrespectively 44.74%, 65.41%, and 80.35%.

Please continue to refer to FIG. 11A. When the value of the weight ratioof curcumin to polyoxyethylene (32) stearate in the tablet comprisingpolyoxyethylene (32) stearate was 5.3, 8.9, or 26.7, the dissolutionrate of curcumin from the tablet at 60 minutes was respectively 77.34%,88.11%, and 89.01%. Among them, the dissolution rate was greater than85% when the value of the weight ratio of curcumin to polyoxyethylene(32) stearate was 8.9 or 26.7. Therefore, the value of the weight ratioof curcumin to polyoxyethylene (32) stearate being 8.9 or 26.7 in thetablet can make the composition comprising epigallocatechin gallate andcurcumin of the present invention meet the criteria of oral dosage formsand promote the bioavailability.

Please refer to FIG. 11B for the same experimental results. In FIG. 11B,“weight ratio of curcumin to polyoxyethylene (32) stearate” in FIG. 11Awas converted to “weight ratio of the active ingredient composition forreducing body weight or body fat to polyoxyethylene (32) stearate.”

The testing results are shown in FIG. 11B. When the value of the weightratio of the active ingredient composition for reducing body weight orbody fat to polyoxyethylene (32) stearate in the tablet comprisingpolyoxyethylene (32) stearate was 9.5, 15.8, or 47.5, the dissolutionrate of curcumin from the tablet at 30 minutes was respectively 44.74%,65.41%, and 80.35%.

Please continue to refer to FIG. 11B. When the value of the weight ratioof the active ingredient composition for reducing body weight or bodyfat to polyoxyethylene (32) stearate in the tablet comprisingpolyoxyethylene (32) stearate was 9.5, 15.8, or 47.5, the dissolutionrate of curcumin from the tablet at 60 minutes was respectively 77.34%,88.11%, and 89.01%. Among them, the dissolution rate was greater than85% when the value of the weight ratio of the active ingredientcomposition for reducing body weight or body fat to polyoxyethylene (32)stearate was 15.8 or 47.5. Therefore, the value of the weight ratio ofthe active ingredient composition for reducing body weight or body fatto polyoxyethylene (32) stearate being 15.8 or 47.5 in the tablet canmake the composition comprising epigallocatechin gallate and curcumin ofthe present invention meet the criteria of oral dosage forms and promotethe bioavailability.

EXAMPLE 8 Animal Experiment II (Drug Administration During ObesityInduction)

The test substances of this experiment were prepared as follows:

Preparing an ME00RS composition: Mixing ME00C1A and an appropriateamount of sterile water to a total concentration of 108.5 mg/mL(milligrams solute per milliliter of solution) of green tea extract andturmeric extract to obtain the ME00RS composition. Wherein, based on thetotal weight of ME00C1A, the green tea extract was 55.5 wt %, and theturmeric extract was 44.5 wt %.

Preparing an ME00R composition: Mixing ME00C1A, piperine, and anappropriate amount of sterile water to a total concentration of 108.5mg/mL of green tea extract and turmeric extract to obtain the ME00Rcomposition. Wherein, the content of green tea extract and the contentof turmeric extract were identical as those of the ME00RS composition.Based on the total weight of the ME00R composition, the piperine was0.1-0.5 wt %. Based on the total volume of the ME00R composition, theconcentration of piperine was 0.525-2.625 mg/mL (milligrams solute permilliliter of solution.)

Preparing an ME00C1B composition: Mixing ME00C1A, piperine, glyceryldibehenate, and an appropriate amount of sterile water to a totalconcentration of 108.5 mg/mL of green tea extract and turmeric extractto obtain the MEOOC1B composition. Wherein, the content of green teaextract and the content of turmeric extract were identical as those ofthe ME00RS composition. Based on the total weight of the ME00C1Bcomposition, the piperine was 0.1-0.5 wt %, and the glyceryl dibehenatewas 0.5-1.2 wt %. Based on the total volume of the ME00C1B composition,the concentration of piperine was 0.525-2.625 mg/mL, and theconcentration of glyceryl dibehenate was 2.625-6.3 mg/mL (milligramssolute per milliliter of solution.)

Preparing an ME00C2B composition: Mixing ME00C1A, piperine,polyoxyethylene (32) stearate, and an appropriate amount of sterilewater to a total concentration of 108.5 mg/mL of green tea extract andturmeric extract to obtain the ME00C2B composition. Wherein, the contentof green tea extract and the content of turmeric extract were identicalas those of the ME00RS composition. Based on the total weight of theME00C2B composition, the piperine was 0.1-0.5 wt %, and thepolyoxyethylene (32) stearate was 0.5-1.2 wt %. Based on the totalvolume of the ME00C2B composition, the concentration of piperine was0.525-2.625 mg/mL, and the concentration of polyoxyethylene (32)stearate was 2.625-6.3 mg/mL (milligrams solute per milliliter ofsolution.)

Preparing an ME00C3B composition: Mixing ME00C1A, piperine, polysorbate80 mixture, and an appropriate amount of sterile water to a totalconcentration of 108.5 mg/mL of green tea extract and turmeric extractto obtain the ME00C3B composition. Wherein, the content of green teaextract and the content of turmeric extract were identical as those ofthe ME00RS composition. Based on the total weight of the ME00C3Bcomposition, the piperine was 0.1-0.5 wt %, and the polysorbate 80mixture was 0.5-1.2 wt %. Based on the total volume of the ME00C3Bcomposition, the concentration of piperine was 0.525-2.625 mg/mL, theconcentration of polysorbate 80 mixture was 2.625-6.3 mg/mL (milligramssolute per milliliter of solution.) Wherein, the polysorbate 80 mixturewas a mixture comprising polysorbate 80 and magnesiumaluminometasilicate.

The concentration of piperine in said ME00R composition, ME00C1Bcomposition, ME00C2B composition, and ME00C3B composition was identical.

The weight percentage of glyceryl dibehenate in said ME00C1B compositionwas identical to that of polyoxyethylene (32) stearate in said ME00C2Bcomposition.

In this experimental example, 7-week old male SD rats were used anddivided into a obesity control group (that is, the HFD group), an ME00Rcomposition of the present invention group, an ME005R group, an ME00C1Bgroup, an ME00C2B group, and an ME00C3B group. Each group included 4rats for experimentation. The rats were fed with high-fat diet for 8consecutive weeks to induce obesity, and during the same period weredaily fed by oral gavage a test substance (the dosing volume of the testsubstance each time was 3 mL per kg of body weight of the rat; the dailydosage of the test substance was 325.5 mg per kg of body weight of therat per day). Rats in the obesity control group were fed equal volumesof sterile water to evaluate the difference in body weight and visceralfat of rats in each group. During the experiment, the body weight andthe average food intake of each rat were recorded weekly. The rats werefasted for 8-12 hours in the evening prior to experiment completion.Then, the rats were sacrificed to weigh their empty body weight, andtheir epididymal fat, perirenal fat, and mesenteric fat were dissectedand weighed to calculate the amount of visceral fat. The relative bodyfat percentage (%) was calculated as follows:

The weight of visceral fat÷the empty body weight=body fat percentage

The body fat percentage÷average of body fat percentage of rats in theobesity control group×100%=relative body fat percentage

The data of each group are expressed as mean±SD. Letters a, b, and cindicate the results of statistical analysis, wherein different lettersindicate significant statistical difference between groups (p<0.05), andidentical letters indicate no significant statistical difference betweengroups (p>0.05).

The experimental results are shown in FIG. 12A. Comparing to the ME00R5group, rats administered with ME00C1B, ME00C2B, or ME00C3B showedsignificantly reduced body weight gain (p<0.05). Therefore, glyceryldibehenate and piperine can significantly promote the weight lossefficacy of the composition of the present invention; polyoxyethylene(32) stearate and piperine can significantly promote the weight lossefficacy of the composition of the present invention; polysorbate 80mixture and piperine can also significantly promote the weight lossefficacy of the composition of the present invention.

The experimental results shown in FIG. 12B also demonstrate that ratsadministered with ME00C1B, ME00C2B, or ME00C3B showed significantlydecreased body fat percentage (p<0.05) comparing to the ME00R5 group.Therefore, glyceryl dibehenate and piperine can significantly promotethe fat loss efficacy of the composition of the present invention;polyoxyethylene (32) stearate and piperine can significantly promote thefat loss efficacy of the composition of the present invention;polysorbate 80 mixture and piperine can also significantly promote thefat loss efficacy of the composition of the present invention.

These experiments demonstrate that excipients can significantly promotethe weight loss efficacy and the fat loss efficacy of the composition ofthe present invention, and increase the bioavailability of thecomposition of the present invention.

EXAMPLE 9 Animal Experiment III (Drug Administration During ObesityInduction)

The test substances of this experiment were prepared as follows:

Preparing an ME00C1B composition: the preparation method was the same asthat of the ME00C1B composition in the Example 8. The ratio of turmericextract to green tea extract in the ME00C1B composition was 4:5.

Preparing an ME00C14 composition: the preparation method was the same asthat of the ME00C1B composition in Example 8. The only difference wasthat the ratio of turmeric extract to green tea extract in the ME00C14composition was 2:1.

Preparing an ME00D11 composition: the preparation method was the same asthat of the ME00C1B composition in Example 8. The only difference wasthat the ratio of turmeric extract to green tea extract in the ME00D11composition was 1:2.

Preparing an ME00D14 composition: the preparation method was the same asthat of the ME00C1B composition in Example 8. The only difference wasthat the ratio of turmeric extract to green tea extract in the ME00D14composition was 1:5.

In this experimental example, 7-week old male SD rats were used anddivided into an obesity control group (that is, the HFD group), anME00C14 composition group, an ME00D11 group, an ME00D14 group, and anME00C1B group. Each group included 4 rats for experimentation. The ratswere fed with high-fat diet for 8 consecutive weeks to induce obesity,and during the same period were daily fed by oral gavage a testsubstance (the dosing volume of the test substance was each time 3 mLper kg of body weight of the rat; the daily dosage of the test substancewas 325.5 mg per kg of body weight of the rat per day). Rats in theobesity control group were fed equal volumes of sterile water toevaluate the difference in body weight and visceral fat of rats in eachgroup. During the experiment, the body weight and the average foodintake of each rat were recorded weekly. The rats were fasted for 8-12hours in the evening prior to experiment completion. Then, the rats weresacrificed to weigh their empty body weight, and their epididymal fat,perirenal fat, and mesenteric fat were dissected and weighed tocalculate the amount of visceral fat. The calculation method was thesame as that of Example 8.

The experimental results are shown in FIG. 13A. Comparing to the obesitycontrol group, rats administered with ME00C14, ME00D11, ME00D14, andME00C1B showed significantly reduced body weight gain (p<0.05).

The experimental results shown in FIG. 13B also demonstrate thatcomparing to the obesity control group, rats administered with ME00C14,ME00D11, and ME00C1B showed significantly decreased body fat percentage(p<0.05).

These experiments demonstrate that specific ratios of green tea extractto turmeric extract can significantly promote the weight loss efficacyand the fat loss efficacy.

EXAMPLE 10 Animal Experiment IV (Drug Administration after ObesityInduction)

The test substances of this experiment were prepared as follows:

Preparing an ME00C4A composition: mixing 250 mg of green tea extract,200 mg of turmeric extract, piperine, polyoxyethylene (40) stearate, andan appropriate amount of sterile water to obtain the ME00C4Acomposition. Wherein, based on the total weight of the ME00C4Acomposition, the piperine was 0.1-0.5 wt %, and the polyoxyethylene (40)stearate was 0.5-1.2 wt %. Based on the total volume of the ME00C4Acomposition, the concentration of piperine was 0.525-2.625 mg/mL, andthe concentration of polyoxyethylene (40) stearate was 2.625-6.3 mg/mL(milligrams solute per milliliter of solution).

In this experimental example, male SD rats were used and divided into anormal diet control group (that is, the NFD-C group), a high-fathigh-cholesterol diet control group (that is, the HFD-C group), and anME00C4A group. Other than the normal diet control group that was fedwith normal diets, rats in the other groups were fed with high-fathigh-cholesterol diet for 8 consecutive weeks to induce obesity, fattyliver, and non-alcoholic steatohepatitis (NASH). Rats in the ME00C4Agroup were daily fed by oral gavage with the ME00C4A composition foreight consecutive weeks (the daily administered dosage was 372 mg per kgof body weight of the rat per day); Rats in the normal diet controlgroup (that is, the NFD-C group) and the high-fat high-cholesterol dietcontrol group (that is, the HFD-C group) were fed with equal volumes ofsterile water. During the experiment, the rats in the high-fathigh-cholesterol diet control group (that is, the HFD-C group) and theME00C4A group were continuously fed with high-fat high-cholesterol diet.The body weight and the average food intake of each rat were recordeddaily. After the experiment was completed, the rats were fasted for 8-10hours. Then, the rats were sacrificed to weigh their empty body weight,and their epididymal fat, perirenal fat, and mesenteric fat weredissected and weighed to calculate the amount of visceral fat. Thecalculation method was the same as that of Example 8. The whole liver ofrat was weighed. Part of the liver tissue was homogenized by ahomogenizer, and the level of fat, cholesterol, and triglyceride wasmeasured by different ELISA kits. Furthermore, the liver was sectionedand histologically stained to evaluate the level of liver inflammationin the rats based on NAFLD Activity Score (NAS; please refer to Table 2for scoring criteria). If the NAFLD Activity Score of the rat is greaterthan or equal to 5, the rat has non-alcoholic steatohepatitis.

Based on the NAFLD Activity Score analysis of the histologically stainedtissues, this experiment had successfully induced fatty liver andnon-alcoholic steatohepatitis in the rats.

Please refer to FIGS. 14A-14B. Comparing to the high-fathigh-cholesterol diet control group (that is, the HFD-C group), ratsadministered with ME00C4A showed significantly reduced relative bodyweight gain and body fat percentage (p<0.05.)

Based on the experimental results, the compositions with excipients ofthe present invention demonstrate significant weight loss efficacy andfat loss efficacy in rats with fatty liver and non-alcoholicsteatohepatitis.

TABLE 2 Scoring criteria of NAFLD Activity Scoring system Steatosisgrade Lobular inflammation Hepatocyte ballooning (0-3) (0-3) (0-2) 0:<5% 0: None 0: None 1: 5-33% 1: <2 foxi/*20 field 1: Mild, few 2: 34-66%2: 2-4 foci/*20 field 2: Moderate-many 3: >66% 3: >4 foxi/*20 fieldNAFLD activity 0-2 not NASH score (NAS): 0-8 3-4 uncertain for NASH 5-8NASH

Non-Alcoholic Steatohepatitis (NASH) Clinical Research Network FibrosisStaging System

Please refer to FIGS. 15A-15D. Comparing to the high-fathigh-cholesterol diet control group (that is, the HFD-C group), ratsadministered with ME00C4A showed significantly decreased liver weight,level of liver fat, level of total liver cholesterol, and level of livertriglyceride (p<0.05).

Based on these experimental results, the compositions with excipients inthe present invention can significantly reduce the liver weight, levelof liver fat, level of liver total cholesterol, and level of livertriglyceride in rats with fatty liver and non-alcoholic steatohepatitis,thereby achieving the efficacy of treating fatty liver and non-alcoholicsteatohepatitis.

The above descriptions are merely the preferred embodiments, and are notlimitations to the present invention in any form; even though thepreferred embodiments of the present invention are disclosed above, theyare not used to limit the present invention by any means. Any personskilled in the art, without deviation from the scope of the technicalplan of the present invention, could use the above disclosed technicalinformation to make equivalently effective embodiments with equivalentchanges by several adjustments or modifications, but any simplemodification, equivalent change, and modification substantially made tothe above embodiments according to the techniques of the presentinvention, while not deviating from the technical plans of the presentinvention, should still belong within the scope of the technical plansof the present invention.

1-33. (canceled)
 34. A composition for reducing body weight or body fat,comprising epigallocatechin gallate (EGCG), curcumin, and apharmaceutically acceptable excipient.
 35. The composition of claim 34,wherein the value of the weight ratio between curcumin and EGCG in thecomposition is 0.32 to 3.2.
 36. The composition of claim 34, wherein thevalue of the weight ratio between curcumin and EGCG in the compositionis 0.4.
 37. The composition of claim 34, wherein the value of the weightratio between curcumin and EGCG in the composition is 3.2.
 38. Thecomposition of claim 34, wherein the pharmaceutically acceptableexcipient comprises polyoxyethylene stearates, piperine, or acombination thereof.
 39. The composition of claim 38, wherein thepolyoxyethylene stearate is polyoxyethylene (32) stearate,polyoxyethylene (40) stearate, or a combination thereof.
 40. Thecomposition of claim 34, wherein the composition further comprisesresveratrol.
 41. The composition of claim 34, wherein the composition isformulated for oral administration or for injection.
 42. A method forreducing body weight or body fat in a subject, the method comprisingadministering to a subject in need thereof an effective amount of thecomposition of claim
 34. 43. The method of claim 42, wherein the valueof the weight ratio between curcumin and EGCG in the composition is 0.32to 3.2.
 44. The method of claim 42, wherein the value of the weightratio between curcumin and EGCG in the composition is 0.4.
 45. Themethod of claim 42, wherein the value of the weight ratio betweencurcumin and EGCG in the composition is 3.2.
 46. The method of claim 42,wherein the pharmaceutically acceptable excipient comprisespolyoxyethylene stearates, piperine, or a combination thereof.
 47. Themethod of claim 46, wherein the polyoxyethylene stearate ispolyoxyethylene (32) stearate, polyoxyethylene (40) stearate, or acombination thereof.
 48. The method of claim 42, wherein the compositionfurther comprises resveratrol.
 49. The method of claim 42, wherein thecomposition is administered to the subject orally or by injection. 50.The method of claim 42, wherein the subject is a human subject.